2-(4-Fluorophenyl)acetyl isocyanate → 4-(4-{3-[2-(4-Fluorophenyl)acetyl]ureido}phenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine

HRID 492926Notes

Reaction equation

HRID 492926 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([N:22]4[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][C:39]([N:41]=[C:42]=[O:43])=[O:40])=[CH:34][CH:33]=1>O1CCCC1>[F:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][C:39]([NH:41][C:42](=[O:43])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:17][CH2:18][CH:19]([N:22]5[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]5)[CH2:20][CH2:21]4)=[O:15])[CH:8]=3)=[CH:29][CH:30]=2)=[O:40])=[CH:36][CH:37]=1

Participants

4

Reactant 2

HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 231533634-(4-Aminophenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine

Product 1

HCID 231532284-(4-{3-[2-(4-Fluorophenyl)acetyl]ureido}phenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridineYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(4-aminophenoxy)-2-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyridine (86.9 mg) in tetrahydrofuran (2.5 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 2.12 ml) at room temperature, followed by stirring for 3 days. The reaction mixture was concentrated under reduced pressure. The resultant residue was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=97:3) to provide the titled compound (22.5 mg, 18%) as white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe resultant residue was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=97:3)

Sources & evidence

ORD record
ord-8a30893712aa43edb3d38f3c9ed9f97d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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